Angiogenesis is a fundamental process required for normal growth and development of tissues, and involves the proliferation of new capillaries from pre-existing blood vessels. Angiogenesis is not only involved in embryonic development and normal tissue growth, repair, and regeneration, but is also involved in the female reproductive cycle, establishment and maintenance of pregnancy, and in repair of wounds and fractures. In addition to angiogenesis, which takes place in healthy individuals, angiogenic events are involved in a number of pathological processes, notably tumor growth and metastasis, and other conditions in which blood vessel proliferation, especially of the microvascular system, is increased, such as diabetic retinopathy, psoriasis and arthropathies. Inhibition of angiogenesis is useful in preventing or alleviating these pathological processes.
Because of the crucial role of angiogenesis in so many physiological and pathological processes, factors involved in the control of angiogenesis have been intensively investigated. A number of growth factors have been shown to be involved in the regulation of angiogenesis. These growth factors include fibroblast growth factors (FGFs), vascular endothelial growth factors (VEGF), platelet-derived growth factor (PDGF), transforming growth factor α (TGFα), and hepatocyte growth factor (HGF) (See, Folkman et al., J. Biol. Chem., 267: 10931-10934 (1992)).
The PDGF and VEGF family of growth factors are similar in that both naturally exist as dimeric forms in order to interact with their specific receptors. Additionally, these families of growth factors and their corresponding receptors are believed to be primarily responsible for stimulation of endothelial cell growth and differentiation, and for certain functions of differentiated cells. It is believed that these factors act via receptor tyrosine kinases (RTKs).
A number of PDGF/VEGF family members have been identified. These include PDGF-A (See, for example, GenBank Accession No. X06374), PDGF-B (See, for example, GenBank Accession No. M12783), PDGF-C (see, e.g., PCT International Application WO 00/18212), PDGF-D (see, e.g., PCT International Application WO 00/027879), VEGF (also known as VEGF-A, or by particular isoform), Placenta growth factor, PlGF (see, e.g., U.S. Pat. No. 5,919,899), VEGF-B (also known as VEGF-related factor (VRF); see, e.g., PCT International Application WO 96/26736 and WO 96/26736), VEGF-C, (see, e.g., U.S. Pat. No. 6,221,839 and WO 98/33917), VEGF-D (also known as c-fos-induced growth factor (FIGF); see, e.g., U.S. Pat. No. 6,235,713 and PCT International Application WO 98/07832), VEGF-E (also known as NZ7 VEGF or OV NZ7; see, e.g., PCT International Application WO 00/025805 and U.S. Patent Publication No. 2003/0113870), NZ2 VEGF (also known as OV NZ2; see, GenBank Accession No. S67520), D1701 VEGF-like protein (see, e.g., GenBank Accession No. AF106020; Meyer et al., EMBO J. 18:363-374), and NZ10 VEGF-like protein (see, e.g., PCT International Application WO 00/25805; Stacker and Achen, Growth Factors, 17:1-11 (1999); Neufeld et al., FASEB J., 13:9-22 (1999); Ferrara, J Mol Med 77:527-543 (1999)).
Type 1 Placental Growth Factor (PlGF-1) is an angiogenic homodimeric glycoprotein. When in dimeric form, PlGF-1 exhibits angiogenic activity. In monomeric form, PlGF-1 is inactive. The complete polynucleotide sequence encoding the PlGF-1 protein, along with its polypeptide sequence, is described in European Patent Publication No. 0 550 519 and PCT International Application WO 92/06194. PlGF-1 binds as a homodimer to its receptor, the fms-like tyrosine kinase Flt-1 receptor. A soluble form of the Flt-1 receptor (sFlt-1) has been identified. sFlt-1 is a splice variant of the Flt-1 receptor which lacks the transmembrane and cytoplasmic domains of the Flt-1 receptor, but contains seven IgG-like domains of the external portion of the receptor. PlGF-1 also binds to the sFlt-1 receptor. Because PlGF-1 plays such an important role in pathological angiogenesis, it has the potential to become a prognostic marker for use in identifying or predicting risk of certain diseases (e.g., cardiovascular disease and hypertensive disorders including hypertension during pregnancy). Additionally, there is no reported biological role for the circulating complex of the PlGF-1 and sFlt-1 proteins bound to each other, therefore the detection of the free (uncomplexed), forms of these proteins could provide potentially more useful clinical information (e.g., published U.S. Patent Application No. 2007-0111326).
Thereupon, there is a need in the art for methods and kits and components thereof that can be employed for monitoring for PlGF-1. Moreover, there is also a need in the art for methods and kits and components thereof that can be employed for monitoring for free PlGF-1. These and other objects of the disclosure will be apparent from the description following herein.